Relationship between Modulator Recognition Factor 2/AT-rich Interaction Domain 5B Gene Variations and Type 2 Diabetes Mellitus or Lipid Metabolism in a Northern Chinese Population

Abstract

Background:Four single nucleotide polymorphisms (SNPs) in the modulator recognition factor 2/AT-rich interaction domain 5B (MRF2/ARID5B) gene located at chromosome 10q21.2 have been shown to be associated with both type 2 diabetes mellitus (T2DM) and coronary artery disease in a Japanese cohort. This study aimed to investigate the relationship between these SNPs (rs2893880, rs10740055, rs7087507, rs10761600) and new-onset T2DM and lipid metabolism in a Northern Chinese population.Methods:This was a case-control study. The rs2893880, rs10740055, rs7087507, and rs10761600 genetic variants were genotyped by SNPscan and analyzed in relation to T2DM susceptibility in 2000 individuals (999 with newly diagnosed T2DM and 1001 controls without diabetes mellitus). Associations between the MRF2/ARID5B genetic models and T2DM were determined by multivariate logistic regression.Results:Regarding the rs10740055 SNP, AA was associated with a higher risk of T2DM compared with codominant-type CC (adjusted by sex, age, and body mass index [BMI], P = 0.041, odds ratio [OR] = 1.421, 95% confidence interval [CI] 1.014–1.991). Meanwhile, AA individuals were at increased risk of presenting with T2DM compared with individuals with CC or a single C (adjusted by sex, age, and BMI, P = 0.034, OR = 1.366, 95% CI 1.023–1.824). With respect to rs10761600, AT contributed to a higher risk of T2DM compared with AA (adjusted by sex, age, and BMI, P = 0.013, OR = 1.585, 95% CI 1.101–2.282), while TT also increased the risk of presenting with T2DM compared with AA or A (adjusted by sex, age, and BMI, P = 0.004, OR = 1.632, 95% CI 1.166–2.284). High-density lipoprotein cholesterol (HDL-C) levels were significantly different among the three genotypes of rs7087507 in the controls (P = 0.048) (GG>GA).Conclusions:The present results identified MRF2/ARID5B as a potential susceptibility gene for new-onset T2DM in a Northern Chinese population, while the rs7087507 SNP was associated with HDL-C levels. Further larger studies are required to validate these findings.

Liraglutide on type 2 diabetes mellitus with nonalcoholic fatty liver disease: A systematic review and meta-analysis of 16 RCTs

“…Their levels are positively correlated with the degree of abnormal lipid metabolism. [ 59 ] HDL-C is a specific molecule with a “ defatting ” effect and ubiquitously reducing in obese diabetic patients. [ 60 ] Its content is also inversely correlated with the degree of abnormal lipid metabolism.…”

Transporters, <b><i>TBC1D4</i></b>, and <b><i>ARID5B</i></b> Variants to Explain Glycated Hemoglobin Variability in Patients with Type 2 Diabetes

“…ARID5B encodes for an AT-rich protein that binds to DNA and aids in histone formation to regulate the transcription of genes involved in adipogenesis and liver development [37]. Variants on ARID5B have shown to impact leukemia susceptibility in Hispanics and T2D in Asians [38, 39]. For example, variant rs1421085 on FTO/IRX3/5 alter ARID5B transcriptional regulation of adipocyte differentiation which in turn accelerates T2D development [40].…”

ARID5B rs10821936 and rs10994982 gene polymorphism and susceptibility to juvenile systemic lupus erythematosus and lupus nephritis

“…Dysregulation of immune system includes immune cells, such as T and B lymphocytes, cytokines such as interleukins, complement, HLA, adhesion molecules and signaling pathways. [16][17][18][19][20][21] The ARID5B gene is located on the long arm of chromosome 10 at position 21.2 and extends from 61,901,254 to 62,096,944 base pairs. The ARID5B gene encodes for the transcriptional factor ARID5B or Mrf-2.…”

“…The ARID5B is widely expressed throughout the human body. 23 Single nucleotide polymorphisms (SNPs) or mutations in the ARID5B gene were reported to be associated with different human diseases, including coronary artery disease (CAD), 20 Type 2 diabetes (T2D), 21 acute lymphoblastic and myeloid leukemia (ALL and AML) especially in children, 22,23 racial disparities of ALL and treatment outcome, 24 autoimmune thyroid disease, 25 RA, 26 and SLE. 7 The most frequent clinical feature in jSLE was renal affection (81.7%), anemia (74%), malar rash (59.6%), and the proliferative LN was more common than nonproliferative (75.3% versus 24.7%).…”